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Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET).

The biodistribution and toxicity of n,n-diethyl-m-toluamide (134623) (DEET), the most commonly used insect repellent in the United States, is reviewed. An estimated 22 percent of the American population is exposed to DEET. Estimates of occupational exposure, occurring in some outdoor workers, range from 442 grams over a 6 month period to 2 kilograms over 7 months. Penetration of human skin has been variably reported as 9 to 56 percent of a topical dose, with approximately 17 percent absorption into the bloodstream. DEET is rapidly absorbed and rapidly, but only partially, eliminated through urinary excretion of hepatic metabolites, with persistent accumulation in the skin. One study of embryotoxicity in mice has not been substantiated by other studies. Animal studies of carcinogenicity and mutagenicity, which have been very limited, yield negative results. Central nervous system symptoms including excitation, shaking, prostration, stiffness of movement, lack of coordination, and gait disturbance have been reported in animal studies. Reports of adverse effects of DEET in humans are uncommon. Rare incidences of sporadic allergic reactions and dermatitis, including sporadic occurrences of scarring bullous dermatitis have been reported. Six cases of encephalopathies in girls, ages 1 to 6 years, have been reported following personal spraying with DEET. Three of these cases resulted in death. Neurologic signs and symptoms, including muscle cramping, insomnia, irritability, depression, and episodes of confusion have been reported by National Park Service workers after exposure to 4 grams or more of DEET per week. The authors postulate that the encephalopathies in children may indicate an age related difference in absorption and identify this as an area in which further research is needed. The authors also identify the need for more research into the carcinogenicity and neurotoxic effects of DEET.